Clonal dynamics and Stereo-seq resolve origin and phenotypic plasticity of adenosquamous carcinoma

被引：3

作者：

Zhao, Ruiying ^{[1
]}

Xu, Yunhua ^{[2
]}

Chen, Yedan ^{[3
]}

Zhang, Jiajun ^{[4
,5
]}

Teng, Fei ^{[5
]}

Liao, Sha ^{[4
,5
]}

Chen, Shengnan ^{[1
]}

Wu, Qian ^{[3
]}

Xiang, Chan ^{[1
]}

Pang, Jiaohui ^{[3
]}

Shang, Zhanxian ^{[1
]}

Zhao, Jikai ^{[1
]}

Bao, Hairong ^{[3
]}

Bao, Hua ^{[3
]}

Shao, Yang ^{[3
,6
]}

Lu, Shun ^{[2
]}

Han, Yuchen ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Pathol, Sch Med, Shanghai 200030, Peoples R China

[2] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai Lung Canc Ctr, Sch Med, Shanghai 200030, Peoples R China

[3] Nanjing Geneseeq Technol Inc, Geneseeq Res Inst, Nanjing 210032, Peoples R China

[4] BGI Res, Chongqing 401329, Peoples R China

[5] BGI Res, Shenzhen 518083, Peoples R China

[6] Nanjing Med Univ, Sch Publ Hlth, Nanjing 211166, Peoples R China

来源：

NPJ PRECISION ONCOLOGY | 2023年 / 7卷 / 01期

基金：

中国国家自然科学基金;

关键词：

SQUAMOUS-CELL CARCINOMA; TYROSINE KINASE INHIBITORS; HISTOLOGIC TRANSFORMATION; LUNG ADENOCARCINOMA; CANCER; RECONSTRUCTION; EXPRESSION; COMPONENTS; RESISTANCE; MECHANISM;

D O I：

10.1038/s41698-023-00430-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The genomic origin and development of the biphasic lung adenosquamous carcinoma (ASC) remain inconclusive. Here, we derived potential evolutionary trajectory of ASC through whole-exome sequencing, Stereo-seq, and patient-derived xenografts. We showed that EGFR and MET activating mutations were the main drivers in ASCs. Phylogenetically, these drivers and passenger mutations found in both components were trunk clonal events, confirming monoclonal origination. Comparison of multiple lesions also revealed closer genomic distance between lymph node metastases and the ASC component with the same phenotype. However, as mutational signatures of EGFR-positive lung squamous carcinomas (LUSCs) were more comparable to EGFR-positive ASCs than to wild-type LUSCs, we postulated different origination of these LUSCs, with ASC being the potential intermediate state of driver-positive LUSCs. Spatial transcriptomic profiling inferred transformation from adenocarcinoma to squamous cell carcinoma, which was then histologically captured in vivo. Together, our results explained the development of ASC and provided insights into future clinical decisions.

引用

页数：14